This is a randomized, double-blind and placebo-controlled study to evaluate the efficacy of zoledronic acid on the biologic incorporation of cementless hip prosthesis in postmenopausal female patients.The study population consists of postmenopausal female patients scheduled for total hip replacement because of degenerative hip osteoarthritis. The patients will receive either a single dose of 5 mg zoledronic acid or placebo intravenously after surgery before hospital discharge. The patients will be followed-up for 1 year. Zoledronic acid therapy has been shown to promote bone ingrowth into porous implants in pre-clinical models. The investigators hypothesis is that zoledronic acid, given as a single intravenous infusion after hip replacement surgery, enhances bone ingrowth into porous surface of cementless hip prostheses. As a primary outcome, the therapy is expected to reduce periprosthetic bone loss measured by DXA. Enhancement of bone ingrowth is expected to increase primary stability of the hip prosthesis and this effect can be detected with high-precision three-dimensional RSA imaging modality and in a faster functional recovery of the patients.

The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

The patients in the active-treatment group will receive a single 5 mg dose of zoledronic acid intravenously just prior to release from the hospital (about 5th day post-surgery) as an adjunct therapy. The control group will receive a placebo (saline) infusion. All infusions will be given 100 ml in volume and infused over a period of 15 minutes with a pre- and post-infusion flush with normal saline.

Detailed Description:

All the patients enrolled in the study will receive the standard of care with respect to surgical prosthetic replacement of the diseased hip. The patients will receive a custom-modified (RSA marked) hydroxyapatite-coated prosthesis with ceramic-on-ceramic bearing surfaces (SYMAX-TRIDENT, Stryker). The prosthesis modification provided by the manufacturer has a CE mark. The patients in the active-treatment group will receive a single 5 mg dose of zoledronic acid intravenously just prior to release from the hospital (about 5th day post-surgery) as an adjunct therapy. The control group will receive a placebo (saline) infusion. The active and placebo infusion vials will be provided by Norvartis Pharmaceutical. After surgery, before the administration of zoledronic acid or placebo, each patient will be re-screened for the level of serum calcium. In the case of postoperative hypocalcemia, the infusion will be postponed for a minimum of 3-4 weeks and the infusion will be given after the repeated measurements of serum calcium. All patients will receive calcium and D-vitamin supplementation throughout the study period. Efficacy will be assessed on the basis of clinical, radiographic (RSA, DXA, Spiral CT, conventional radiography) and laboratory criteria. The clinical benefit of zoledronic acid therapy is defined in terms of faster functional recovery, which will be analyzed in two ways: (1) the functional outcome (muscle strength, gait analysis and pedometry) will be repeatedly evaluated before and after surgery, and (2) the subjective outcome of the procedure as well as the general health assessment will be determined at each follow-up visits using standardized outcome measures. The primary objective of this study is to test whether a single infusion of zoledronic acid reduces periprosthetic bone loss measured by DXA at 12 months. Statistical significance of differences in periprosthetic bone mineral density between active-treatment and placebo groups will be analyzed using repeated analysis of variance.

Eligibility

Ages Eligible for Study:

20 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Degenerative hip osteoarthritis as the indication for hip replacement

Postmenopausal female patient

Age of at least 20 years

Signed Informed Consent

Exclusion Criteria:

Evidence of secondary osteoporosis

Clinical or laboratory evidence of hepatic or renal disease

Disorders of parathyroid function, or D-vitamin metabolism

History of malignancy, radiotherapy, or chemotherapy for malignancy (except for basal cell carcinoma of the skin) within the past 5 years

No metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing

Administration for more than 7 days of drugs, which may interfere with bone metabolism:

cumulative dose of 500 mg of prednisone or equivalent within the last 6 months

calcitonin within the last 6 months

bisphosphonates for 30 days or more within the last 12 months

bone therapeutic doses of fluoride for 30 days or more within the last 24 months

Rheumatoid arthritis or any other inflammatory arthritis

History of osteogenesis imperfecta, multiple myeloma, or Paget's disease

Active primary hyperparathyroidism

History of uveitis, iritis, or chronic conjunctivitis

History of retinopathy or nephropathy, especially in the presence of uncontrollable IDDM (Hb1AC > 10%)

AST or ALT > 2X the upper limit of normal

ALP > 1.5X the upper limit of normal

Serum creatine > 2 mg/dl

Creatine clearance < 40 ml/min

Serum calcium > 11.0 mg/dL and < 8mg/dL

Serum 25(OH)D < 15 ng/ml

In subjects with HIV must have a plasma HIV-1 RNA level of < 5000, a CD4+ count of > 100 cells/mm3m and be receiving stable ART for a minimum of 12 weeks prior study entry, with no plan at study entry to significantly alter ART

Allergy to zoledronic acid

Severe dental problems or current dental infections or with recent or impending dental surgery within three months of dosing

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01218035